Glaucoma, which some estimate affects 2 million adults over 40, is an impairment of vision caused by too much fluid pressure within the eye.
Surgical treatment for glaucoma does not represent a long term cure. While it is effective, it is also expensive and traumatic, and some surgeons will use surgery only as a last resort.
Carbonic anhydrase inhibitors, prescribed orally work well to treat this disease, but they carry a host of side effects, from nausea to kidney stones. The preferred method of treatment for the disease is instillation by drops to the eye; however, carbonic anhydrase inhibitors have not proven effective when given this way.
Glaucoma stems from an excess of fluid behind the cornea, the three-layered tissue that acts as a window to let light enter. Fluid carrying nutrients such as potassium and glucose constantly wash the inside of the cornea to keep it healthy, much as tears wash the outside of the cornea.
In some middle-aged adults fluids build up faster than can be absorbed back into the blood, for one of two reasons: the ciliary body (a tiny tissue behind the iris) may excrete too much fluid, or the fluid may not drain off at the normal rate.
Either way, the excess fluid damages the optic nerve. At first a glaucoma victim usually experiences a subtle loss of peripheral vision--objects will seem to disappear from certain spots to the side. But glaucoma often leads to middle-age blindness.
Unfortunately, the two approaches to general drug usage in treating glaucoma--topical (dropped into the eye) and oral--each have a peculiar set of side effects.
To make the long journey, oral drugs must be dosed in very high concentration. One class of drugs, called carbonic anhydrase inhibitors when taken orally slow the formation of fluid by inhibiting a chemical reaction at the ciliary body. Along with their well-tested effectiveness, comes nausea, tingling in fingers and toes and other side effects. Oral drugs generally do not, however, cause side effects in the eye.
Certain topical drugs, other than carbonic anhydrase inhibitors, e.g., pilocarpine, while causing less systemic effects, can cause severe headaches and constrict the pupil, making the daytime appear dark.
Accordingly, there is a real and continuing need to develop an inhibitor drug that can be dropped into the eye instead of swallowed, thereby avoiding the present side effects.
It is a primary objective of the present invention to develop a highly effective topical carbonic anhydrase inhibitor drug (which previously is only effective orally) for treatment of glaucoma to reduce intraocular eye pressure, and at the same time, avoid the systemic side effects, commonly caused by oral drugs.
Another objective of the present invention is to develop a drug for topical treatment of glaucoma, which is not only effective, but which will also pass through the three layered cornea and still be effective enough to work on the ciliary body.
Another objective of the present invention is to develop a highly effective, topical drug treatment for glaucoma which is substantially non-harmful to the eye when topically applied.
An even further objective of the present invention is to develop an eye treating topical composition which is effective for glaucoma treatment.
A still further objective is to provide a convenient method of synthesis of certain new and novel compounds which are highly effective topical treatments for glaucoma.
A further specific objective of the present invention is to provide as a novel compound, N-methyl-2-acetylamino-1,3,4-thiadiazole-5-sulfonamide (methyl acetazolamide), which in pharmaceutically effective amounts is a highly effective topical composition for eye drop treatment of glaucoma.
The method and manner of achieving each of the above objectives, as well as others, will become apparent from the detailed description of the invention which follows hereinafter.